Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4Y17PY)

DOT Name Integrin alpha-IIb (ITGA2B)
Synonyms GPalpha IIb; GPIIb; Platelet membrane glycoprotein IIb; CD antigen CD41
Gene Name ITGA2B
Related Disease
Glanzmann thrombasthenia ( )
Obsolete Glanzmann's thrombasthenia ( )
Platelet-type bleeding disorder 16 ( )
Acute megakaryoblastic leukemia ( )
Acute myelogenous leukaemia ( )
Acute myocardial infarction ( )
Adult glioblastoma ( )
Advanced cancer ( )
Aplastic anemia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Atrial fibrillation ( )
Bacterial endocarditis ( )
Bernard-Soulier syndrome ( )
Beta thalassemia ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Childhood myelodysplastic syndrome ( )
Clear cell renal carcinoma ( )
Coagulation defect ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Glanzmann thrombasthenia 1 ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Idiopathic thrombocytopenic purpura ( )
Infective endocarditis ( )
Intracerebral hemorrhage ( )
Juvenile idiopathic arthritis ( )
Melanoma ( )
Metastatic malignant neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Renal cell carcinoma ( )
Schizophrenia ( )
Myelodysplastic syndrome ( )
Neoplasm ( )
Neuroblastoma ( )
Autosomal dominant macrothrombocytopenia ( )
Hepatitis C virus infection ( )
Immune thrombocytopenia ( )
Rheumatoid arthritis ( )
Thrombocytopenia ( )
UniProt ID
ITA2B_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
1DPK ; 1DPQ ; 1KUP ; 1KUZ ; 1M8O ; 1S4W ; 1TYE ; 2K1A ; 2K9J ; 2KNC ; 2MTP ; 2N9Y ; 2VC2 ; 2VDK ; 2VDL ; 2VDM ; 2VDN ; 2VDO ; 2VDP ; 2VDQ ; 2VDR ; 3FCS ; 3FCU ; 3NID ; 3NIF ; 3NIG ; 3T3M ; 3T3P ; 3ZDX ; 3ZDY ; 3ZDZ ; 3ZE0 ; 3ZE1 ; 3ZE2 ; 4CAK ; 4Z7N ; 4Z7O ; 4Z7Q ; 5HDB ; 6V4P ; 7KN0 ; 7L8P ; 7LA4 ; 7SC4 ; 7SFT ; 7TCT ; 7TD8 ; 7THO ; 7TMZ ; 7TPD ; 7U60 ; 7U9F ; 7U9V ; 7UBR ; 7UCY ; 7UDG ; 7UDH ; 7UE0 ; 7UFH ; 7UH8 ; 7UJE ; 7UJK ; 7UK9 ; 7UKO ; 7UKP ; 7UKT ; 8T2U ; 8T2V
Pfam ID
PF01839 ; PF08441 ; PF20805 ; PF20806 ; PF00357
Sequence
MARALCPLQALWLLEWVLLLLGPCAAPPAWALNLDPVQLTFYAGPNGSQFGFSLDFHKDS
HGRVAIVVGAPRTLGPSQEETGGVFLCPWRAEGGQCPSLLFDLRDETRNVGSQTLQTFKA
RQGLGASVVSWSDVIVACAPWQHWNVLEKTEEAEKTPVGSCFLAQPESGRRAEYSPCRGN
TLSRIYVENDFSWDKRYCEAGFSSVVTQAGELVLGAPGGYYFLGLLAQAPVADIFSSYRP
GILLWHVSSQSLSFDSSNPEYFDGYWGYSVAVGEFDGDLNTTEYVVGAPTWSWTLGAVEI
LDSYYQRLHRLRGEQMASYFGHSVAVTDVNGDGRHDLLVGAPLYMESRADRKLAEVGRVY
LFLQPRGPHALGAPSLLLTGTQLYGRFGSAIAPLGDLDRDGYNDIAVAAPYGGPSGRGQV
LVFLGQSEGLRSRPSQVLDSPFPTGSAFGFSLRGAVDIDDNGYPDLIVGAYGANQVAVYR
AQPVVKASVQLLVQDSLNPAVKSCVLPQTKTPVSCFNIQMCVGATGHNIPQKLSLNAELQ
LDRQKPRQGRRVLLLGSQQAGTTLNLDLGGKHSPICHTTMAFLRDEADFRDKLSPIVLSL
NVSLPPTEAGMAPAVVLHGDTHVQEQTRIVLDCGEDDVCVPQLQLTASVTGSPLLVGADN
VLELQMDAANEGEGAYEAELAVHLPQGAHYMRALSNVEGFERLICNQKKENETRVVLCEL
GNPMKKNAQIGIAMLVSVGNLEEAGESVSFQLQIRSKNSQNPNSKIVLLDVPVRAEAQVE
LRGNSFPASLVVAAEEGEREQNSLDSWGPKVEHTYELHNNGPGTVNGLHLSIHLPGQSQP
SDLLYILDIQPQGGLQCFPQPPVNPLKVDWGLPIPSPSPIHPAHHKRDRRQIFLPEPEQP
SRLQDPVLVSCDSAPCTVVQCDLQEMARGQRAMVTVLAFLWLPSLYQRPLDQFVLQSHAW
FNVSSLPYAVPPLSLPRGEAQVWTQLLRALEERAIPIWWVLVGVLGGLLLLTILVLAMWK
VGFFKRNRPPLEEDDEEGE
Function
Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface.
Tissue Specificity
Isoform 1 and isoform 2 are expressed in platelets and megakaryocytes, but not in reticulocytes. Not detected in Jurkat, nor in U937 cell lines . Isoform 3 is expressed in prostate adenocarcinoma, as well as in several erythroleukemia, prostate adenocarcinoma and melanoma cell lines, including PC-3, DU-145, HEL, WM983A, WM983B and WM35. Not detected in platelets, nor in normal prostate (at protein level) .
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
PI3K-Akt sig.ling pathway (hsa04151 )
Focal adhesion (hsa04510 )
ECM-receptor interaction (hsa04512 )
Platelet activation (hsa04611 )
Neutrophil extracellular trap formation (hsa04613 )
Hematopoietic cell lineage (hsa04640 )
Regulation of actin cytoskeleton (hsa04810 )
Cytoskeleton in muscle cells (hsa04820 )
Human papillomavirus infection (hsa05165 )
Pathways in cancer (hsa05200 )
Small cell lung cancer (hsa05222 )
Hypertrophic cardiomyopathy (hsa05410 )
Arrhythmogenic right ventricular cardiomyopathy (hsa05412 )
Dilated cardiomyopathy (hsa05414 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
Integrin cell surface interactions (R-HSA-216083 )
ECM proteoglycans (R-HSA-3000178 )
Integrin signaling (R-HSA-354192 )
GRB2 (R-HSA-354194 )
p130Cas linkage to MAPK signaling for integrins (R-HSA-372708 )
Signal transduction by L1 (R-HSA-445144 )
MAP2K and MAPK activation (R-HSA-5674135 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by high-kinase activity BRAF mutants (R-HSA-6802948 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glanzmann thrombasthenia DISFGGTG Definitive Autosomal recessive [1]
Obsolete Glanzmann's thrombasthenia DISFH7MK Definitive Autosomal recessive [2]
Platelet-type bleeding disorder 16 DISPUR84 Definitive Autosomal dominant [1]
Acute megakaryoblastic leukemia DIS0JX3M Strong Biomarker [3]
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [4]
Acute myocardial infarction DISE3HTG Strong Biomarker [5]
Adult glioblastoma DISVP4LU Strong Biomarker [6]
Advanced cancer DISAT1Z9 Strong Biomarker [7]
Aplastic anemia DISJRSC0 Strong Biomarker [8]
Arteriosclerosis DISK5QGC Strong Genetic Variation [9]
Atherosclerosis DISMN9J3 Strong Genetic Variation [9]
Atrial fibrillation DIS15W6U Strong Altered Expression [10]
Bacterial endocarditis DIS920N0 Strong Biomarker [11]
Bernard-Soulier syndrome DISLD1FU Strong Altered Expression [12]
Beta thalassemia DIS5RCQK Strong Genetic Variation [13]
Breast cancer DIS7DPX1 Strong Biomarker [14]
Breast carcinoma DIS2UE88 Strong Biomarker [14]
Cardiac failure DISDC067 Strong Biomarker [15]
Childhood myelodysplastic syndrome DISMN80I Strong Biomarker [8]
Clear cell renal carcinoma DISBXRFJ Strong Genetic Variation [16]
Coagulation defect DIS9X3H6 Strong Biomarker [17]
Colon cancer DISVC52G Strong Altered Expression [18]
Colon carcinoma DISJYKUO Strong Altered Expression [18]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [19]
Congestive heart failure DIS32MEA Strong Biomarker [15]
Coronary atherosclerosis DISKNDYU Strong Genetic Variation [20]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [20]
Glanzmann thrombasthenia 1 DIS8UDNZ Strong Autosomal recessive [21]
Glioblastoma multiforme DISK8246 Strong Biomarker [6]
Glioma DIS5RPEH Strong Biomarker [6]
Hepatocellular carcinoma DIS0J828 Strong Genetic Variation [22]
Idiopathic thrombocytopenic purpura DISFKGJU Strong Altered Expression [23]
Infective endocarditis DIS88NSA Strong Biomarker [11]
Intracerebral hemorrhage DISC81BT Strong Biomarker [24]
Juvenile idiopathic arthritis DISQZGBV Strong Biomarker [25]
Melanoma DIS1RRCY Strong Altered Expression [26]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [27]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [20]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [28]
Renal cell carcinoma DISQZ2X8 Strong Genetic Variation [16]
Schizophrenia DISSRV2N Strong Genetic Variation [29]
Myelodysplastic syndrome DISYHNUI moderate Biomarker [8]
Neoplasm DISZKGEW moderate Biomarker [28]
Neuroblastoma DISVZBI4 moderate Genetic Variation [30]
Autosomal dominant macrothrombocytopenia DISUTMSW Supportive Autosomal dominant [31]
Hepatitis C virus infection DISQ0M8R Limited Genetic Variation [32]
Immune thrombocytopenia DISVCBNS Limited Biomarker [33]
Rheumatoid arthritis DISTSB4J Limited Altered Expression [34]
Thrombocytopenia DISU61YW Limited CausalMutation [35]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Eptifibatide DMQXTJS Approved Integrin alpha-IIb (ITGA2B) increases the Surgical and medical procedures ADR of Eptifibatide. [49]
Abciximab DMJO6GV Approved Integrin alpha-IIb (ITGA2B) increases the Surgical and medical procedures ADR of Abciximab. [49]
Tirofiban DMQG17S Approved Integrin alpha-IIb (ITGA2B) increases the Surgical and medical procedures ADR of Tirofiban. [49]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Integrin alpha-IIb (ITGA2B). [36]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Integrin alpha-IIb (ITGA2B). [37]
Rosiglitazone DMILWZR Approved Rosiglitazone affects the expression of Integrin alpha-IIb (ITGA2B). [38]
Aspirin DM672AH Approved Aspirin decreases the expression of Integrin alpha-IIb (ITGA2B). [39]
Etoposide DMNH3PG Approved Etoposide increases the expression of Integrin alpha-IIb (ITGA2B). [40]
Nicotine DMWX5CO Approved Nicotine decreases the expression of Integrin alpha-IIb (ITGA2B). [41]
Dactinomycin DM2YGNW Approved Dactinomycin increases the expression of Integrin alpha-IIb (ITGA2B). [40]
Asasantin DMCZIHT Approved Asasantin decreases the expression of Integrin alpha-IIb (ITGA2B). [39]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Integrin alpha-IIb (ITGA2B). [42]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Integrin alpha-IIb (ITGA2B). [43]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Integrin alpha-IIb (ITGA2B). [44]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Integrin alpha-IIb (ITGA2B). [45]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Integrin alpha-IIb (ITGA2B). [46]
Arachidonic acid DMUOQZD Investigative Arachidonic acid increases the expression of Integrin alpha-IIb (ITGA2B). [47]
Rutin DMEHRAJ Investigative Rutin increases the expression of Integrin alpha-IIb (ITGA2B). [48]
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⏷ Show the Full List of 15 Drug(s)

References

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